Design of a magnetic resonance imaging-based screening program for early diagnosis of prostate cancer: preliminary results of a randomized controlled trial-Prostate Cancer Secondary Screening in Sapienza (PROSA).

OBJECTIVES: The main objective is to propose an MRI-based screening protocol, investigating the role of MRI without the injection of contrast media (bi-parametric MRI, bpMRI) as a secondary prevention test for prostate cancer (PCa) early diagnosis, comparing MRI with the prostate specific antigen (PSA) test. For this reason, preliminary results of Prostate Cancer Secondary Screening in Sapienza (PROSA) are presented, to investigate the efficiency of an MRI-based screening protocol. PROSA is a prospective, randomized, single-center study. To date, 351 men have been enrolled and blindly randomized into two different arms: (A) Men underwent a bpMRI regardless of their PSA values (175); (B) Men followed as per clinical practice: those with increased PSA (61) were referred to bpMRI, while those with normal PSA (112) were not. Men who screened positive on MRI were directed to MR-directed targeted biopsy. On arm A, 4 clinically significant PCa have been detected, while none was found on arm B (p = 0.046). To evaluate the efficiency of the screening protocol, we calculated the experimental event rate (EER, 3.6%), control event rate (CER, 1.2%.), absolute risk reduction (ARR, 2.5%), and number needed to treat (NNT, 40.3). PROSA represents an interesting experience in the field of imaging-based PCa screening. The preliminary data from this trial highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. Further data will finally validate the most appropriate screening program. CLINICAL RELEVANCE STATEMENT: PROSA depicts an interesting experience in the field of research focused on imaging-based prostate cancer screening. Its preliminary data highlight the promising role of non-contrast MRI as a screening tool for early detection of PCa. KEY POINTS: • Promotion of an MRI-based screening protocol, investigating the role of non-contrast MRI as a secondary prevention test for prostate cancer early diagnosis, comparing MRI with PSA test. • Prostate Cancer Secondary Screening in Sapienza (PROSA) represents an interesting experience in the field of research focused on imaging-based prostate cancer screening; its preliminary results indicate that it is possible to use non-contrast MRI as a screening tool for early detection of PCa. • This new approach to PCa screening could facilitate the early diagnosis of clinically significant prostate cancer while reducing the number of unnecessary prostate biopsies and the detection of clinically insignificant prostate cancer.

Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction.

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

Biobanks: The unmet need in heart failure management.

Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies. The institution of biobanks may represent the game changer in HF scenario, providing a collection of human biological materials with the related medical and epidemiological data fueling the development of personalized therapeutic approach and fostering current and/or future research projects.

Exploratory study on the endogenous ouabain in idiopathic pulmonary arterial hypertension patients.

INTRODUCTION: Endogenous ouabain (EO) is a steroid hormone secreted by the adrenal glands associated with adverse cardiovascular outcomes. However, EO plays other roles as brain protection against traumatic injury and seems involved in the adaptive response to hypoxia. Recently, we detected, for the first time, EO in a healthy human group of acute hypoxia and diving animals. METHODS: This study complements the above as we considered a human model of chronic hypoxia. The aim is to detect EO in five idiopathic pulmonary arterial hypertension patients. RESULTS AND DISCUSSION: We found that these patients had higher plasma concentrations of EO than control subjects. In addition, EO plasma concentrations were negatively correlated with the mean pulmonary arterial pressure and total pulmonary vascular resistance. The results could suggest that high concentrations of EO are predictive of better adaptation of the right ventricular afterload. CONCLUSION: Although the results are preliminary, they can represent a helpful hint for future investigations for possible therapeutic and diagnostic approaches.

Early Routine Biomarkers of SARS-CoV-2 Morbidity and Mortality: Outcomes from an Emergency Section.

BACKGROUND: COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2, a virus belonging to the Coronaviridae family. This disease has spread rapidly around the world and soon became an international public health emergency leading to an unpredicted pressure on the hospital emergency units. Early routine blood biomarkers could be key predicting factors of COVID-19 morbidity and mortality as suggested for C-reactive protein (CRP), IL-6, prothrombin and D-dimer. This study aims to identify other early routine blood biomarkers for COVID-19 severity prediction disclosed directly into the emergency section. METHODS: Our research was conducted on 156 COVID-19 patients hospitalized at the Sapienza University Hospital "Policlinico Umberto I" of Rome, Italy, between March 2020 and April 2020 during the paroxysm's initial phase of the pandemic. In this retrospective study, patients were divided into three groups according to their outcome: (1) emergency group (patients who entered the emergency room and were discharged shortly after because they did not show severe symptoms); (2) intensive care unit (ICU) group (patients who attended the ICU after admission to the emergency unit); (3) the deceased group (patients with a fatal outcome who attended the emergency and, afterward, the ICU units). Routine laboratory tests from medical records were collected when patients were admitted to the emergency unit. We focused on Aspartate transaminase (AST), Alanine transaminase (ALT), Lactate dehydrogenase (LDH), Creatine kinase (CK), Myoglobin (MGB), Ferritin, CRP, and D-dimer. RESULTS: As expected, ANOVA data show an age morbidity increase in both ICU and deceased groups compared with the emergency group. A main effect of morbidity was revealed by ANOVA for all the analyzed parameters with an elevation between the emergency group and the deceased group. Furthermore, a significant increase in LDH, Ferritin, CRP, and D-dimer was also observed between the ICU group and the emergency group and between the deceased group and ICU group. Receiver operating characteristic (ROC) analyses confirmed and extended these findings. CONCLUSIONS: This study suggests that the contemporaneous presence of high levels of LDH, Ferritin, and as expected, CRP, and D-dimer could be considered as potential predictors of COVID-19 severity and death.

Molecular Identification of New Cases of Human Dirofilariosis (Dirofilaria repens) in Italy.

(1) Dirofilariosis is a vector-borne parasitic disease mainly in domestic and wild carnivores caused by Dirofilaria (Noctiella) repens, which is endemic in many countries of the Old World, and D. immitis, which has a worldwide distribution. In recent years, an increase in the number of human cases has been reported, suggesting that dirofilariosis is an emergent zoonosis. Here, we describe further cases (N = 8), observed in Central Italy during the years 2018-2019. (2) Molecular diagnosis was performed on: (i) live worms extracted from ocular conjunctiva, cheek, and calf muscle; (ii) histological sections of surgically removed nodules from parenchymal lung, coccyx, and breast. (3) Sequence analysis (650-bp) of the mitochondrial cytochrome oxidase subunit I gene (mtDNA cox1) showed a match of 100% with the sequences of D. repens previously deposited in GenBank. ELISA test to detect IgG against filarial antigens was performed on four patients' sera and resulted positive in two patients who showed ocular and subcutaneous dirofilariosis, respectively. Microfilariae have been never detected in the peripheral blood of the patients. (4) The occurrence of N = 8 new cases of human D. repens-infections observed in a two-year period suggests an increased circulation of the parasite in Italy. Therefore, dirofilariosis should be included in differential diagnosis in patients presenting subcutaneous and/or pulmonary nodules. Molecular diagnosis of the etiological agents is fundamental. Specific serological diagnosis needs to be improved in future research work.

Ozone as adjuvant support in the treatment of COVID-19: A preliminary report of probiozovid trial.

The evaluation of new therapeutic resources against coronavirus disease 2019 (COVID-19) represents a priority in clinical research considering the minimal options currently available. To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. PROBIOZOVID is an ongoing, interventional, randomized, prospective, and double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone-autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-ozone administration for 7 days. All patients were treated with ad interim best available therapy. The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, hematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8.3% for ozone group and 10% for controls. Ozone therapy did not significantly influence inflammation markers, hematology profile, and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although did not reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity.

Right Ventricular Strain Curve Morphology and Outcome in Idiopathic Pulmonary Arterial Hypertension.

OBJECTIVES: The purpose of this study was to explore speckle tracking echocardiographic right ventricular (RV) post-systolic strain patterns and their clinical relevance in idiopathic pulmonary arterial hypertension (PAH). BACKGROUND: The imaging of RV diastolic function in PAH remains incompletely understood. METHODS: Speckle tracking echocardiography of RV post-systolic strain recordings were examined in 108 consecutive idiopathic patients with PAH. Each of them underwent baseline clinical, hemodynamic, and complete echocardiographic evaluation and follow-up. RESULTS: In total, 3 post-systolic strain patterns derived from the mid-basal RV free wall segments were identified. Pattern 1 was characterized by prompt return of strain-time curves to baseline after peak systolic negativity, like in normal control subjects. Pattern 2 was characterized by persisting negativity of strain-time curves well into diastole, before an end-diastolic returning to baseline. Pattern 3 was characterized by a slow return of strain-time curves to baseline during diastole. The 3 patterns corresponded respectively to mild PH, more advanced PH but with still preserved RV function, and PH with obvious end-stage right heart failure. Patterns were characterized by optimal reproducibility when complementary to quantitative measurement of right ventricular longitudinal early diastolic strain rate (RVLSR-E), and right ventricular longitudinal late diastolic strain rate (RVLSR-A) (Cohen's κ = 0.88; p = 0.0001). Multivariable models for clinical worsening prediction demonstrated that the addition of RV post-systolic patterns to clinical and hemodynamic variables significantly increased their prognostic power (0.78 vs. 0.66; p < 0.001). Freedom from clinical worsening rates at 1 and 2 years from baseline were, respectively, 100% and 93% for Pattern 1; 80% and 55% for Pattern 2; and 60% and 33% for Pattern 3. CONCLUSIONS: Speckle tracking echocardiography allows for the identification of 3 phenotypically distinct, reproducible, and clinically meaningful RV strain-derived post-systolic patterns.

Clinical implications of idiopathic pulmonary arterial hypertension phenotypes defined by cluster analysis.

BACKGROUND: >Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters. METHODS: Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence. RESULTS: The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3. CONCLUSIONS: Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

The importance of right ventricular evaluation in risk assessment and therapeutic strategies: Raising the bar in pulmonary arterial hypertension.

Pulmonary arterial hypertension is an obstructive pulmonary vasculopathy that leads to increased pulmonary vascular resistance, right ventricular overload and failure, and death. Patients' clinical status and prognosis depend mostly on the capability of the right ventricle to adapt to the increased afterload, maintain function, and preserve cardiac output. As a result, reducing the hemodynamic burden of the right ventricle should be a key target of current treatments, along with improvement in WHO functional class, 6-minute walk distance, and rates of hospitalization. However, physicians still find it challenging to integrate the evaluation of right ventricular function into widely accepted clinical parameters in order to stratify patients more accurately. This limitation is very relevant, since higher-risk patients are more likely to benefit from a more aggressive therapeutic approach. We analyzed the hemodynamic burden in pulmonary arterial hypertension, the importance of echocardiographic evaluation of the right ventricle, the impact of current treatments on hemodynamic parameters, and the identification of patients who are more likely to benefit from a more aggressive therapeutic approach.

Exercise energy expenditure in patients with idiopathic pulmonary arterial hypertension: Impact on clinical severity and survival.

Patient with idiopathic pulmonary hypertension (IPAH) develop peripheral inefficiency which could lead to an increase total energy expenditure and that could have a significant prognostic impact. To test the hypothesis, fifty-five consecutive stable IPAH patients (mean age 51±17 years) and 24 matched controls underwent an incremental exercise test and followed for a 5 years' period. Total energy expenditure was assessed as the ratio between total [Formula: see text] uptake (during both effort and recovery) and total external work ( [Formula: see text] ). Patients with IPAH had a lower exercise capacity and a significantly higher [Formula: see text] than controls ( [Formula: see text] 0.33 ± 0.09 ml/j vs 0.22 ± 0.04 ml/j, p < 0.0001). Among patients, [Formula: see text] was higher in whom died during follow up compared to survivors (0.41 ± 0.11 ml/j vs 0.30 ± 0.06 ml/j, p < 0.0001). In multivariate Cox regression analysis [Formula: see text] , gender, PETCO2 peak, [Formula: see text] were independent risk factors for death. Patients with IPAH have shown a less efficient muscular oxygen utilization than controls. Notably the high energy expenditure has a relevant independent prognostic impact.

The added value of cardiopulmonary exercise testing in the follow-up of pulmonary arterial hypertension.

BACKGROUND: The added value of cardiopulmonary exercise testing (CPET) in the follow-up of patients with stable pulmonary arterial hypertension (PAH) remains undefined. METHODS: Idiopathic, heritable, and drug-induced PAH patients free from clinical worsening (CW) after 1 year of treatment were enrolled in derivation (n = 80) and validation (n = 80) cohorts at an interval of 6 years and followed for 3 years. Prognostic models were constructed and validated in low-risk patients in World Health Organization (WHO) Functional Class I or II with cardiac index (CI) ≥2.5 liters/min/m2 and right atrial pressure (RAP) <8 mm Hg. Discrimination and calibration were assessed. RESULTS: Forty-one derivation cohort patients had CW (51.2%) during 722 ± 349 days. Changes (∆) in WHO classification and CI and absolute value of RAP were independent predictors of CW. With addition of CPET variables, peak oxygen uptake (VO2 peak) and ∆CI independently improved the power of the prognostic model. Receiver operating characteristic (ROC)-derived cut-off values for ∆CI and VO2 peak were 0.40 liter/min/m2 and 15.7 ml/kg/min (≥60% predicted value), respectively. Twenty-nine validation cohort patients had CW (36.2%) during 710 ± 282 days. Different combinations of cut-off values of VO2 peak and ∆CI defined 4 groups. The event-free survival rates at 1, 2, and 3 years were 100%, 100%, and 100%, respectively, for the high ∆CI with high VO2 peak combination; 100%, 88%, and 71% for low ∆CI/high VO2 peak; 80%, 54%, and 40% for high ∆CI/low VO2 peak; and 72%, 54%, and 33% for low ∆CI/low VO2 peak. CONCLUSIONS: The combinations of baseline VO2 peak and change in CI during follow-up is important in prognostication of low-risk patients with idiopathic, heritable, and drug-induced PAH.

Prognostic significance of the echocardiographic estimate of pulmonary hypertension and of right ventricular dysfunction in acute decompensated heart failure. A pilot study in HFrEF patients.

BACKGROUND: Mortality following an admission for acute decompensated heart failure (ADHF) is high and risk stratification in this context remains a challenge. The objective of the present study was to assess whether a simple echocardiographic assessment of pulmonary hypertension (PH) and/or of right ventricular (RV) dysfunction is associated with cardiovascular events in a 1-year follow-up after hospital discharge. METHODS AND RESULTS: The present prospective longitudinal study included 214 patients admitted to hospital with a cardiologist-adjudicated diagnosis of ADHF and a left ventricular ejection fraction (LVEF) at echocardiography < 40%. Echocardiography was performed at admission and at discharge and included pulmonary artery systolic pressure (PASP) and RV function as defined by the tricuspid annular plane systolic displacement (TAPSE). The primary end-point was the combination of all-cause mortality and re-hospitalization for worsening heart failure at 1 year after hospital discharge. During an average follow-up period of 230 ±â€¯130 days, 40 patients died and 41 patients underwent re-hospitalization due to ADHF. At multivariate analysis the independent predictors were LVEF, PASP at discharge and creatinine plasma levels (all p < 0.001). At ROC analysis the best threshold of PASP to discriminate low-risk from high-risk patients was 40 mm Hg. CONCLUSIONS: In ADHF patients with reduced LVEF, PH at discharge is a pivotal prognostic feature to predict morbidity/mortality within the first year after the acute episode.

The importance of right ventricular function in patients with pulmonary arterial hypertension.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a progressive, life-threatening, and incurable disease. Its prognosis is based on right ventricular (RV) function. Therefore, adequate assessment of RV function is mandatory. Areas covered: This article presents the case of a patient with PAH in which the traditional diagnostic approach did not provide a complete assessment of RV function. The authors show how the analysis of other parameters yielded additional information that improved the management of this patient. Expert commentary: Despite current treatments, PAH often worsens due to progressive RV dysfunction. Appropriate assessment of RV function may facilitate the early identification of patients at risk of RV function impairment. More aggressive treatment of PAH might delay progression of the disease. Traditional risk stratification, which is based on New York Heart Association/World Health Organization (NYHA/WHO) functional class evaluation, the 6-minute walk test, and right heart catheterization, proves insufficient in many PAH patients, as it does not provide complete information about RV function. Thus, further parameters are required. Analysis of RV function, in addition to echocardiography and cardiopulmonary exercise testing, may add relevant prognostic information and improve therapy.

Influence of various therapeutic strategies on right ventricular morphology, function and hemodynamics in pulmonary arterial hypertension.

BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies. METHODS: Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters. RESULTS: At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively. CONCLUSIONS: In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results.

[Oral combination therapy for the treatment of patients with pulmonary arterial hypertension: what evidence from long-term studies?] / La terapia di combinazione orale nel trattamento dei pazienti con ipertensione arteriosa polmonare: quali evidenze dagli studi a lungo termine?

The introduction of specific drugs for the treatment of pulmonary arterial hypertension over the last 20 years has led to an improvement of clinical and hemodynamic conditions and prognosis of affected patients. The use of combination therapy has made it possible to act simultaneously on several biological pathways involved in the etiopathogenesis of the disease. However, although the diagnosis and management have radically changed in recent years, the disease remains progressive and often fatal. The purpose of this paper is to review and discuss the results of the main clinical trials and the future perspectives of combination strategies for the treatment of pulmonary arterial hypertension.

Prognostic relevance of right heart reverse remodeling in idiopathic pulmonary arterial hypertension.

BACKGROUND: Right ventricular (RV) failure is a major determinant of symptoms and shortened survival in pulmonary arterial hypertension (PAH). This study assessed the prognostic relevance of increased right heart (RH) dimensions determined by echocardiography and RH reverse remodeling (RHRR) with targeted therapies in idiopathic PAH (IPAH). METHODS: The study prospectively monitored 102 therapy-naïve IPAH patients for the presence of clinical worsening. Baseline evaluation included RH catheterization and echocardiography. RHRR at the 1-year follow-up was defined by a decrease in RV end-diastolic area, right atrial area, and the left ventricular systolic eccentricity index. RESULTS: At the 1-year follow-up, 18 of 102 patients (17.6%) presented with RHRR. A decrease in pulmonary vascular resistance was the only independent determinant of RHRR. The 94 surviving patients were monitored for 995 ± 529 days. RHRR was an independent prognostic factor and significantly improved the power of the prognostic model based on traditional clinical and hemodynamic parameters. The respective event-free survival rates at 1, 3, and 5 years were 94%, 94%, and 94% in patients with RHRR and 75%, 55%, and 24% in those without RHRR (p = 0.0001). Interestingly, RHRR was able to further stratify patients' risk assessment through the Registry to Evaluate Early And Long-term PAH Disease Management risk score. CONCLUSIONS: RHRR after 1 year of treatment is an independent predictor of prognosis in IPAH. The likelihood of RHRR is proportional to decreased pulmonary vascular resistance.

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension.

Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known.104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peak V'O2 ).A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r2=0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r2=0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r2=0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peak V'O2 (r2=0.53; p=0.001).A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH.

Prognostic relevance of pulmonary arterial compliance after therapy initiation or escalation in patients with pulmonary arterial hypertension.

BACKGROUND: Conventional hemodynamic parameters are considered to be the gold standard indices of outcome in pulmonary arterial hypertension (PAH); on the contrary, few data support the hypothesis that the pulsatile component of right ventricular afterload provides important prognostic information. The aim of the study was to investigate the prognostic significance of pulmonary arterial compliance (PCa) after therapy initiation or escalation in PAH patients. METHODS: A cohort of 419 consecutive PAH patients (308 naive and 111 prevalent) underwent right heart catheterisation (RHC) prior to initiating or escalating PAH-targeted therapy. RHC was repeated in 255 patients (61%) after 4 to 12months of therapy as 62 patients (15%) died and 102 (24%) did not undergo a follow-up RHC within the first year. RESULTS: After the follow-up RHC, 63 patients died over a median follow-up period of 39months. At multivariate analysis, age>50years old, male gender, etiology associated with systemic sclerosis, persistence of WHO class III/IV, and reduced PCa at follow-up RHC were the independent parameters significantly associated with poor prognosis. At ROC analysis, the optimal cut-off point of PCa to predict survival was 1.4mL/mmHg (AUC 0.73, sensitivity 81.8%, specificity 58.8%). CONCLUSIONS: In PAH patients hospitalized to initiate or to escalate PAH-specific therapy, failure to improve PCa after therapy is a strong hemodynamic predictor of poor prognosis.